<p><b>A</b> Z-transformed coherence spectrum between nucleus accumbens and fron... more <p><b>A</b> Z-transformed coherence spectrum between nucleus accumbens and frontal scalp electrode Fz. The horizontal dotted line (Z = 2.8) indicates the threshold of the coherence calculated from data shuffled over trials (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0138685#sec003" target="_blank">Methods</a>). Coherence values between 4 Hz and 14 Hz are above this threshold. Electrodes Fz and Oz are circled. <b>B</b> Coherence in the theta-band showed a strong frontal topography and a weaker parieto-occipital topography. <b>C</b> Coherence in the alpha-band was strongest around frontal electrodes. The *’s indicate scalp electrodes that were significantly coherent between 4–14 Hz with nucleus accumbens when controlling for multiple comparisons over electrodes and frequency bins using a cluster randomization approach. A strong frontal and a weaker parietal cluster emerged. <b>D</b> Example of coherence in the parietal cluster. The Z-transformed coherence spectrum between nucleus accumbens and occipitoparietal scalp electrode Oz is depicted.</p
<p><b>A</b> The <i>time</i> by <i>frequency</i> interac... more <p><b>A</b> The <i>time</i> by <i>frequency</i> interaction (F(1, 5) = 20.92, p<0.01, Cohen’sf = 0.17) indicates that there was a significant theta band increase poststimulus compared to prestimulus Granger causality (t(5) = 3.52, p<0.05). No such change was present in the alpha-band. In the poststimulus window, Granger causality in the theta band was significantly stronger than in the alpha band (t(5) = 4.27, p<0.01). <b>B</b> The ANOVA showed a significant frequency by directionality interaction (F(1, 5) = 9.68, p<0.05, Cohen’s f = 0.17). In post-hoc tests, we found that the granger-causal influence from nucleus accumbens on cortex was stronger in the theta-band than in the alpha-band (t(5) = 4.84, p<0.01). In contrast, there was no significant difference in Granger causality in the alpha-band between cortex-to-nucleus accumbens and nucleus accumbens-to-cortex direction (t(5) = 1.75, p = 0.14). However, for five out of six subjects Granger estimates in the alpha-band were stronger for the cortex-to-nucleus accumbens direction than the other way around (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0138685#pone.0138685.g005" target="_blank">Fig 5</a>). Data are represented as mean ± SEM. * = p<0.05, ** = p<0.01. = p<0.01.</p
Recent advances in neuroscience and technology have made it possible to record from large assembl... more Recent advances in neuroscience and technology have made it possible to record from large assemblies of neurons and to decode their activity to extract information. At the same time, available methods to stimulate the brain and influence ongoing processing are also rapidly expanding. These developments pave the way for advanced neurotechnological applications that directly read from, and write to, the human brain. While such technologies are still primarily used in restricted therapeutic contexts, this may change in the future once their performance has improved and they become more widely applicable. Here, we provide an overview of methods to interface with the brain, speculate about potential applications, and discuss important issues associated with a neurotechnologically assisted future.
Cyberpsychology, behavior and social networking, 2017
The retrospective and subjective nature of clinical interviews is an important shortcoming of cur... more The retrospective and subjective nature of clinical interviews is an important shortcoming of current psychiatric diagnosis. Consequently, there is a clear need for objective and standardized tools. Virtual reality (VR) can be used to achieve controlled symptom provocation, which allows direct assessment for the clinician. We developed a video VR game to provoke and assess obsessive-compulsive disorder (OCD) symptoms in a standardized and controlled environment. The first objective was to evaluate if the VR game is capable of provoking symptoms in OCD patients as opposed to healthy controls. The second objective was to evaluate the tolerability of the VR game in OCD patients. The VR game was created using a first-person perspective and confronted patients with 15 OCD-specific items, while simultaneously measuring OCD symptoms, including the number of compulsions, anxiety, tension, uncertainty, and urge to control. In this pilot study, eight patients and eight healthy controls perfor...
Neuroimaging research has revealed that emotion processing recruits a widespread neural network i... more Neuroimaging research has revealed that emotion processing recruits a widespread neural network including the dorsal anterior cingulate cortex (dACC), hippocampus, and amygdala. Recent studies have started to investigate the role of the primary inhibitory neurotransmitter γ-aminobutyric acid (GABA) on brain function, but little is known about the influences of GABA on this emotion circuitry. Using magnetic resonance spectroscopy, we investigated the role of GABA levels in the dACC on emotion processing by presenting emotional and neutral pictures to 68 healthy male participants during functional magnetic resonance imaging. Results revealed opposing associations of dACC GABA levels and neural activity. GABA levels were positively correlated with blood oxygen level dependent (BOLD) responses to emotional stimuli in the amygdala and to emotional and neutral stimuli in the hippocampus. In contrast, GABA levels were negatively correlated with BOLD responses for the comparison between pos...
To investigate whether early nonresponse to antipsychotic treatment of acute mania predicts treat... more To investigate whether early nonresponse to antipsychotic treatment of acute mania predicts treatment failure and, if so, to establish the best definition or criterion of an early nonresponse. Short-term efficacy studies assessing antipsychotics that were submitted to the Dutch Medicines Evaluation Board during an 11-year period as part of the marketing authorization application for the indication of acute manic episode of bipolar disorder. Pharmaceutical companies provided their raw patient data, which enabled us to perform an individual patient data meta-analysis. All double-blind, randomized, placebo-controlled trials assessing the efficacy of antipsychotics for acute manic episode of bipolar disorder were included (10 trials). All patients with data available for completer analysis (N = 1,243), symptom severity scores on the Young Mania Rating Scale (YMRS) at weeks 0, 1, and 2 and at study end point (week 3 or 4). The a priori chances of nonresponse and nonremission at study end...
P.4.d. Anxiety disorders, OCD, stress related disorders and treatment − Treatment (clinical) cont... more P.4.d. Anxiety disorders, OCD, stress related disorders and treatment − Treatment (clinical) contributed to the reduction of global Y-BOCS rather than that of obsession. There was significant reduction in Y-BOCS for compulsion (<0.05), but no significant change in Y-BOCS for obsession. CGI at the second week of treatment (3.17) and CGI at the end of treatment (3.23) also showed significant changes, in comparison with CGI at baseline (4.38). Additional significant changes in BDI, BAI, SCL-90-R, and MMSE were not seen. Any significant adverse effects were not reported. Conclusion: These findings suggest that 1 Hz rTMS over the SMA can be an efficient and safe therapeutic tool as an add-on therapy in treatment-refractory patients of OCD. Also, there was no significant change in cognitive function after rTMS. However, there are several limitations of this study including a small number of participants and lack of control group. Further controlled studies in larger samples are required to confirm the effect of rTMS in OCD. P.4.d.003 Cost-effectiveness of deep brain stimulation versus treatment as usual for obsessivecompulsive disorder
Neuromodulation: Technology at the Neural Interface, 2016
Deep brain stimulation (DBS) revolutionized the treatment of movement disorders such as Parkinson... more Deep brain stimulation (DBS) revolutionized the treatment of movement disorders such as Parkinson's disease and is emerging into a promising tool as therapy for psychiatric disorders. Although DBS has been approved by the Food and Drug Administration (FDA) and the European authorities for treatment-resistant obsessive-compulsive disorder (OCD) for more than 4 years, its application still is controversial (1) and regarded with suspicion. National as well as international guidelines for OCD are rather reluctant to implement DBS, which is, if at all, recommended in the context of controlled clinical trials only (2). Indeed, scientific studies, including larger sample sizes, are definitely needed to tackle the still unsolved questions of response prediction or to determine the mechanisms of action underlying the therapeutic effects of DBS. Yet, large effect sizes (3) and meta-analytical results (4,5) underline that DBS constitutes a valid option for a subgroup of severely affected and treatment-resistant OCDpatients. Therefore, we advocate the extended integration of DBS into the overall therapeutic concept and propose a sequential approach based on the neurobiological underpinnings of OCD. OCD is amongst the most common and disabling mental disorders worldwide (6). It is characterized by recurrent and intrusive thoughts and/or repetitive behaviors that are time consuming, cause remarkable distress and often are perceived as inappropriate by the patient who, most often unsuccessfully tries to resist (7). International guidelines agree on cognitive behavioral therapy (CBT) being the first line treatment for OCD (2), thereby focusing on the exposure to anxiety-inducing situations while at the same time preventing the engagement in fear relieving compulsions (8). In more severe cases, or for patients suffering predominantly from obsessions or comorbid depressive symptoms, CBT should be combined with pharmacological interventions. The efficacy of serotonin reuptake inhibitors (SSRI) and clomipramine is well established in the treatment of OCD. SSRIs usually show a higher tolerability and are therefore given priority. If treatment response is unsatisfactory an augmentation with atypical antipsychotics or dual medications as venlafaxine should be considered (9). These therapeutic strategies are based on different concepts of the pathogenesis of OCD. Even though studies have shown, that CBT also influences the neurobiological substrate of OCD (10,11), it primarily addresses the psychological aspects via behavioral alterations and deconditioning, whereas pharmacotherapy aims to modulate neurobiological or neurochemical aspects of OCD in the first place. These different approaches are not contradictory but complementary. Typically OCD manifests in the second or third decade of life and often takes a chronic persistent course. Particularly early
Background: Accumulating evidence points towards the involvement of autoimmune mechanisms in the ... more Background: Accumulating evidence points towards the involvement of autoimmune mechanisms in the pathophysiology of some subgroups of obsessive-compulsive disorder (OCD). This study was carried out to investigate whether obsessive-compulsive disorder is associated with altered activity of the immune system, and whether these changes are related to particular clinical characteristics.Methods: Ex vivo production of TNF-α, IL-4, IL-6, IL-10, and IFN-γ in whole blood cultures, and NK-cell activity and peripheral blood NK cell-, monocytes-, T-cell-, and B-cell- percentages were measured in 50 medication-free outpatients with OCD and 25 controls.Results: In OCD patients, we found a significant decrease in production of TNF-α (p &lt; 0.0001) and NK-activity (p = 0.002) in comparison with controls. No significant differences were observed in the other immune variables. Patients with first-degree relatives with OCD had significant lower NK-activity than patients who had no relatives with OCD (p = 0.02), and patients with a childhood onset of OCD had significantly lower number of NK-cells than patients with a late onset (p= 0.003).Conclusions: Changes in TNF-α and NK activity suggest a potential role of altered immune function in the pathophysiology of obsessive-compulsive disorder.
Neurobiological research of obsessive–compulsive disorder (OCD) has rarely taken in account the c... more Neurobiological research of obsessive–compulsive disorder (OCD) has rarely taken in account the context dependent evocation of obsessive–compulsive symptoms. To bypass this obstacle, this study investigated neurobiological parameters during a standardized disgust provocation paradigm in patients with OCD and healthy controls. Ten OCD patients and 10 healthy controls were exposed to 9 disgust related items using a standardized provocation paradigm. Catecholamines and cortisol in plasma and lipopolysaccharide (LPS) stimulated levels of TNF-α and IL-6 by peripheral leucocytes were assessed along with severity of obsessive–compulsive symptoms, disgust, and anxiety levels using Visual Analogue Scales prior, during and after a provocation paradigm. Noradrenalin levels increased, while LPS stimulated TNF-α and IL-6 by peripheral leucocytes decreased during exposure to disgust related objects in OCD patients but not in healthy controls. Cortisol levels were not affected by exposure neither in patients nor in controls, but overall cortisol levels of OCD patients were increased compared to controls. In conclusion, our data suggests that symptom provocation in OCD patients with contamination fear is accompanied by alterations in the immune and neuroendocrine systems but does not affect cortisol levels.
The expanding field of lateral skull-base surgery is reviewed. The rapid evolution of this subspe... more The expanding field of lateral skull-base surgery is reviewed. The rapid evolution of this subspecialty of otolaryngology--head and neck surgery has occurred subsequent to the primary postgraduate training of many practitioners of our specialty. Furthermore, it can be difficult for many resident physicians to acquire concise, up-to-date references pertaining to this area of subspecialization. This article is designed to provide a succinct, up-to-date review of the field of lateral skull-base surgery. The current literature is reviewed. Lateral skull-base surgery is a rapidly evolving discipline involving neurologists and neurosurgeons in the resection of complex lesions of the skull base that had previously been difficult or impossible to adequately access. Otolaryngologists,via the subspecialty of neurotology, have been leaders in developing and applying the different lateral skull-base approaches. This article categorizes the various lateral skull-base approaches, outlines the pri...
Obsessive-compulsive disorder (OCD) is a psychiatric disorder consisting of obsessions and compul... more Obsessive-compulsive disorder (OCD) is a psychiatric disorder consisting of obsessions and compulsions. Over the past two decades it has been suggested that OCD might be related to the functioning of brain serotonin systems, mainly because of the anti-obsessional efficacy of selective serotonin reuptake inhibitors (SSRIs). Though the efficacy of SSRIs suggests a role of the serotonergic system in OCD, the
Background: While the usefulness of clomipramine and SSRIs in obsessive-compulsive disorder (OCD)... more Background: While the usefulness of clomipramine and SSRIs in obsessive-compulsive disorder (OCD) has been established, the efficacy of SNRIs remains to be determined. This report describes the first, randomized, double blind comparison study of an SNRI in patients with OCD. The current study compares the efficacy and tolerability of venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI) with paroxetine, a selective serotonin reuptake inhibitor (SSRI). Method: One hundred fifty patients with primary OCD according to DSM-IV criteria, were randomly assigned in a 12-week, double-blind trial to receive dosages titrated upward to 300 mg/day of venlafaxine (n=75) or 60 mg/day of paroxetine (n=75). Primary efficacy was assessed by the change from baseline on the Yale-Brown obsessive-compulsive scale (Y-BOCS). Other assessments throughout the trial included the Padua inventory revised (PI-R), the Hamilton depression rating scale (HDRS), and Hamilton anxiety rating scale (HAS). Results: An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean decrease on the Y-BOCS of 7.24-7.5 in the venlafaxine group and of 7.94-5.3 in the paroxetine group. In both treatment groups a responder rate (decrease>35% on the Y-BOCS) of approximately 40% was found. There were no significant differences between venlafaxine and paroxetine as regards response, or responder rates. The incidence of adverse events for venlafaxine and paroxetine was comparable. The most common events for venlafaxine were somnolence, insomnia, dry mouth, and sweating, and for paroxetine somnolence, sweating, nausea and headache. Conclusion: These results show that venlafaxine was equally effective to paroxetine in treating patients with OCD. SNRIs, like venlafaxine may be a useful therapy for obsessive-compulsive patients but are not superior to SSRIs.
<p><b>A</b> Z-transformed coherence spectrum between nucleus accumbens and fron... more <p><b>A</b> Z-transformed coherence spectrum between nucleus accumbens and frontal scalp electrode Fz. The horizontal dotted line (Z = 2.8) indicates the threshold of the coherence calculated from data shuffled over trials (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0138685#sec003" target="_blank">Methods</a>). Coherence values between 4 Hz and 14 Hz are above this threshold. Electrodes Fz and Oz are circled. <b>B</b> Coherence in the theta-band showed a strong frontal topography and a weaker parieto-occipital topography. <b>C</b> Coherence in the alpha-band was strongest around frontal electrodes. The *’s indicate scalp electrodes that were significantly coherent between 4–14 Hz with nucleus accumbens when controlling for multiple comparisons over electrodes and frequency bins using a cluster randomization approach. A strong frontal and a weaker parietal cluster emerged. <b>D</b> Example of coherence in the parietal cluster. The Z-transformed coherence spectrum between nucleus accumbens and occipitoparietal scalp electrode Oz is depicted.</p
<p><b>A</b> The <i>time</i> by <i>frequency</i> interac... more <p><b>A</b> The <i>time</i> by <i>frequency</i> interaction (F(1, 5) = 20.92, p<0.01, Cohen’sf = 0.17) indicates that there was a significant theta band increase poststimulus compared to prestimulus Granger causality (t(5) = 3.52, p<0.05). No such change was present in the alpha-band. In the poststimulus window, Granger causality in the theta band was significantly stronger than in the alpha band (t(5) = 4.27, p<0.01). <b>B</b> The ANOVA showed a significant frequency by directionality interaction (F(1, 5) = 9.68, p<0.05, Cohen’s f = 0.17). In post-hoc tests, we found that the granger-causal influence from nucleus accumbens on cortex was stronger in the theta-band than in the alpha-band (t(5) = 4.84, p<0.01). In contrast, there was no significant difference in Granger causality in the alpha-band between cortex-to-nucleus accumbens and nucleus accumbens-to-cortex direction (t(5) = 1.75, p = 0.14). However, for five out of six subjects Granger estimates in the alpha-band were stronger for the cortex-to-nucleus accumbens direction than the other way around (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0138685#pone.0138685.g005" target="_blank">Fig 5</a>). Data are represented as mean ± SEM. * = p<0.05, ** = p<0.01. = p<0.01.</p
Recent advances in neuroscience and technology have made it possible to record from large assembl... more Recent advances in neuroscience and technology have made it possible to record from large assemblies of neurons and to decode their activity to extract information. At the same time, available methods to stimulate the brain and influence ongoing processing are also rapidly expanding. These developments pave the way for advanced neurotechnological applications that directly read from, and write to, the human brain. While such technologies are still primarily used in restricted therapeutic contexts, this may change in the future once their performance has improved and they become more widely applicable. Here, we provide an overview of methods to interface with the brain, speculate about potential applications, and discuss important issues associated with a neurotechnologically assisted future.
Cyberpsychology, behavior and social networking, 2017
The retrospective and subjective nature of clinical interviews is an important shortcoming of cur... more The retrospective and subjective nature of clinical interviews is an important shortcoming of current psychiatric diagnosis. Consequently, there is a clear need for objective and standardized tools. Virtual reality (VR) can be used to achieve controlled symptom provocation, which allows direct assessment for the clinician. We developed a video VR game to provoke and assess obsessive-compulsive disorder (OCD) symptoms in a standardized and controlled environment. The first objective was to evaluate if the VR game is capable of provoking symptoms in OCD patients as opposed to healthy controls. The second objective was to evaluate the tolerability of the VR game in OCD patients. The VR game was created using a first-person perspective and confronted patients with 15 OCD-specific items, while simultaneously measuring OCD symptoms, including the number of compulsions, anxiety, tension, uncertainty, and urge to control. In this pilot study, eight patients and eight healthy controls perfor...
Neuroimaging research has revealed that emotion processing recruits a widespread neural network i... more Neuroimaging research has revealed that emotion processing recruits a widespread neural network including the dorsal anterior cingulate cortex (dACC), hippocampus, and amygdala. Recent studies have started to investigate the role of the primary inhibitory neurotransmitter γ-aminobutyric acid (GABA) on brain function, but little is known about the influences of GABA on this emotion circuitry. Using magnetic resonance spectroscopy, we investigated the role of GABA levels in the dACC on emotion processing by presenting emotional and neutral pictures to 68 healthy male participants during functional magnetic resonance imaging. Results revealed opposing associations of dACC GABA levels and neural activity. GABA levels were positively correlated with blood oxygen level dependent (BOLD) responses to emotional stimuli in the amygdala and to emotional and neutral stimuli in the hippocampus. In contrast, GABA levels were negatively correlated with BOLD responses for the comparison between pos...
To investigate whether early nonresponse to antipsychotic treatment of acute mania predicts treat... more To investigate whether early nonresponse to antipsychotic treatment of acute mania predicts treatment failure and, if so, to establish the best definition or criterion of an early nonresponse. Short-term efficacy studies assessing antipsychotics that were submitted to the Dutch Medicines Evaluation Board during an 11-year period as part of the marketing authorization application for the indication of acute manic episode of bipolar disorder. Pharmaceutical companies provided their raw patient data, which enabled us to perform an individual patient data meta-analysis. All double-blind, randomized, placebo-controlled trials assessing the efficacy of antipsychotics for acute manic episode of bipolar disorder were included (10 trials). All patients with data available for completer analysis (N = 1,243), symptom severity scores on the Young Mania Rating Scale (YMRS) at weeks 0, 1, and 2 and at study end point (week 3 or 4). The a priori chances of nonresponse and nonremission at study end...
P.4.d. Anxiety disorders, OCD, stress related disorders and treatment − Treatment (clinical) cont... more P.4.d. Anxiety disorders, OCD, stress related disorders and treatment − Treatment (clinical) contributed to the reduction of global Y-BOCS rather than that of obsession. There was significant reduction in Y-BOCS for compulsion (<0.05), but no significant change in Y-BOCS for obsession. CGI at the second week of treatment (3.17) and CGI at the end of treatment (3.23) also showed significant changes, in comparison with CGI at baseline (4.38). Additional significant changes in BDI, BAI, SCL-90-R, and MMSE were not seen. Any significant adverse effects were not reported. Conclusion: These findings suggest that 1 Hz rTMS over the SMA can be an efficient and safe therapeutic tool as an add-on therapy in treatment-refractory patients of OCD. Also, there was no significant change in cognitive function after rTMS. However, there are several limitations of this study including a small number of participants and lack of control group. Further controlled studies in larger samples are required to confirm the effect of rTMS in OCD. P.4.d.003 Cost-effectiveness of deep brain stimulation versus treatment as usual for obsessivecompulsive disorder
Neuromodulation: Technology at the Neural Interface, 2016
Deep brain stimulation (DBS) revolutionized the treatment of movement disorders such as Parkinson... more Deep brain stimulation (DBS) revolutionized the treatment of movement disorders such as Parkinson's disease and is emerging into a promising tool as therapy for psychiatric disorders. Although DBS has been approved by the Food and Drug Administration (FDA) and the European authorities for treatment-resistant obsessive-compulsive disorder (OCD) for more than 4 years, its application still is controversial (1) and regarded with suspicion. National as well as international guidelines for OCD are rather reluctant to implement DBS, which is, if at all, recommended in the context of controlled clinical trials only (2). Indeed, scientific studies, including larger sample sizes, are definitely needed to tackle the still unsolved questions of response prediction or to determine the mechanisms of action underlying the therapeutic effects of DBS. Yet, large effect sizes (3) and meta-analytical results (4,5) underline that DBS constitutes a valid option for a subgroup of severely affected and treatment-resistant OCDpatients. Therefore, we advocate the extended integration of DBS into the overall therapeutic concept and propose a sequential approach based on the neurobiological underpinnings of OCD. OCD is amongst the most common and disabling mental disorders worldwide (6). It is characterized by recurrent and intrusive thoughts and/or repetitive behaviors that are time consuming, cause remarkable distress and often are perceived as inappropriate by the patient who, most often unsuccessfully tries to resist (7). International guidelines agree on cognitive behavioral therapy (CBT) being the first line treatment for OCD (2), thereby focusing on the exposure to anxiety-inducing situations while at the same time preventing the engagement in fear relieving compulsions (8). In more severe cases, or for patients suffering predominantly from obsessions or comorbid depressive symptoms, CBT should be combined with pharmacological interventions. The efficacy of serotonin reuptake inhibitors (SSRI) and clomipramine is well established in the treatment of OCD. SSRIs usually show a higher tolerability and are therefore given priority. If treatment response is unsatisfactory an augmentation with atypical antipsychotics or dual medications as venlafaxine should be considered (9). These therapeutic strategies are based on different concepts of the pathogenesis of OCD. Even though studies have shown, that CBT also influences the neurobiological substrate of OCD (10,11), it primarily addresses the psychological aspects via behavioral alterations and deconditioning, whereas pharmacotherapy aims to modulate neurobiological or neurochemical aspects of OCD in the first place. These different approaches are not contradictory but complementary. Typically OCD manifests in the second or third decade of life and often takes a chronic persistent course. Particularly early
Background: Accumulating evidence points towards the involvement of autoimmune mechanisms in the ... more Background: Accumulating evidence points towards the involvement of autoimmune mechanisms in the pathophysiology of some subgroups of obsessive-compulsive disorder (OCD). This study was carried out to investigate whether obsessive-compulsive disorder is associated with altered activity of the immune system, and whether these changes are related to particular clinical characteristics.Methods: Ex vivo production of TNF-α, IL-4, IL-6, IL-10, and IFN-γ in whole blood cultures, and NK-cell activity and peripheral blood NK cell-, monocytes-, T-cell-, and B-cell- percentages were measured in 50 medication-free outpatients with OCD and 25 controls.Results: In OCD patients, we found a significant decrease in production of TNF-α (p &lt; 0.0001) and NK-activity (p = 0.002) in comparison with controls. No significant differences were observed in the other immune variables. Patients with first-degree relatives with OCD had significant lower NK-activity than patients who had no relatives with OCD (p = 0.02), and patients with a childhood onset of OCD had significantly lower number of NK-cells than patients with a late onset (p= 0.003).Conclusions: Changes in TNF-α and NK activity suggest a potential role of altered immune function in the pathophysiology of obsessive-compulsive disorder.
Neurobiological research of obsessive–compulsive disorder (OCD) has rarely taken in account the c... more Neurobiological research of obsessive–compulsive disorder (OCD) has rarely taken in account the context dependent evocation of obsessive–compulsive symptoms. To bypass this obstacle, this study investigated neurobiological parameters during a standardized disgust provocation paradigm in patients with OCD and healthy controls. Ten OCD patients and 10 healthy controls were exposed to 9 disgust related items using a standardized provocation paradigm. Catecholamines and cortisol in plasma and lipopolysaccharide (LPS) stimulated levels of TNF-α and IL-6 by peripheral leucocytes were assessed along with severity of obsessive–compulsive symptoms, disgust, and anxiety levels using Visual Analogue Scales prior, during and after a provocation paradigm. Noradrenalin levels increased, while LPS stimulated TNF-α and IL-6 by peripheral leucocytes decreased during exposure to disgust related objects in OCD patients but not in healthy controls. Cortisol levels were not affected by exposure neither in patients nor in controls, but overall cortisol levels of OCD patients were increased compared to controls. In conclusion, our data suggests that symptom provocation in OCD patients with contamination fear is accompanied by alterations in the immune and neuroendocrine systems but does not affect cortisol levels.
The expanding field of lateral skull-base surgery is reviewed. The rapid evolution of this subspe... more The expanding field of lateral skull-base surgery is reviewed. The rapid evolution of this subspecialty of otolaryngology--head and neck surgery has occurred subsequent to the primary postgraduate training of many practitioners of our specialty. Furthermore, it can be difficult for many resident physicians to acquire concise, up-to-date references pertaining to this area of subspecialization. This article is designed to provide a succinct, up-to-date review of the field of lateral skull-base surgery. The current literature is reviewed. Lateral skull-base surgery is a rapidly evolving discipline involving neurologists and neurosurgeons in the resection of complex lesions of the skull base that had previously been difficult or impossible to adequately access. Otolaryngologists,via the subspecialty of neurotology, have been leaders in developing and applying the different lateral skull-base approaches. This article categorizes the various lateral skull-base approaches, outlines the pri...
Obsessive-compulsive disorder (OCD) is a psychiatric disorder consisting of obsessions and compul... more Obsessive-compulsive disorder (OCD) is a psychiatric disorder consisting of obsessions and compulsions. Over the past two decades it has been suggested that OCD might be related to the functioning of brain serotonin systems, mainly because of the anti-obsessional efficacy of selective serotonin reuptake inhibitors (SSRIs). Though the efficacy of SSRIs suggests a role of the serotonergic system in OCD, the
Background: While the usefulness of clomipramine and SSRIs in obsessive-compulsive disorder (OCD)... more Background: While the usefulness of clomipramine and SSRIs in obsessive-compulsive disorder (OCD) has been established, the efficacy of SNRIs remains to be determined. This report describes the first, randomized, double blind comparison study of an SNRI in patients with OCD. The current study compares the efficacy and tolerability of venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI) with paroxetine, a selective serotonin reuptake inhibitor (SSRI). Method: One hundred fifty patients with primary OCD according to DSM-IV criteria, were randomly assigned in a 12-week, double-blind trial to receive dosages titrated upward to 300 mg/day of venlafaxine (n=75) or 60 mg/day of paroxetine (n=75). Primary efficacy was assessed by the change from baseline on the Yale-Brown obsessive-compulsive scale (Y-BOCS). Other assessments throughout the trial included the Padua inventory revised (PI-R), the Hamilton depression rating scale (HDRS), and Hamilton anxiety rating scale (HAS). Results: An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean decrease on the Y-BOCS of 7.24-7.5 in the venlafaxine group and of 7.94-5.3 in the paroxetine group. In both treatment groups a responder rate (decrease>35% on the Y-BOCS) of approximately 40% was found. There were no significant differences between venlafaxine and paroxetine as regards response, or responder rates. The incidence of adverse events for venlafaxine and paroxetine was comparable. The most common events for venlafaxine were somnolence, insomnia, dry mouth, and sweating, and for paroxetine somnolence, sweating, nausea and headache. Conclusion: These results show that venlafaxine was equally effective to paroxetine in treating patients with OCD. SNRIs, like venlafaxine may be a useful therapy for obsessive-compulsive patients but are not superior to SSRIs.
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